Li G, Higdon R, Kukull W A, Peskind E, Van Valen Moore K, Tsuang D, van Belle G, McCormick W, Bowen J D, Teri L, Schellenberg G D, Larson E B
Department of Psychiatry and Behavioral Science, University of Washington, Seattle, USA.
Neurology. 2004 Nov 9;63(9):1624-8. doi: 10.1212/01.wnl.0000142963.90204.58.
To assess the association between statin therapy and risk of Alzheimer disease (AD) in a prospective cohort study with documented statin exposure and incident dementia.
This is a prospective, cohort study of statin use and incident dementia and probable AD. A cohort of 2,356 cognitively intact persons, aged 65 and older, were randomly selected from a health maintenance organization (HMO), and were assessed biennially for dementia. Statin use was identified using the HMO pharmacy database. A proportional hazards model with statin use as a time-dependent covariate was used to assess the statin-dementia/AD association.
Among 312 participants with incident dementia, 168 had probable AD. The unadjusted hazard ratios (HRs) with statin use were 1.33 (95% CI 0.95 to 1.85) for all-cause dementia and 0.90 (CI 0.54 to 1.51) for probable AD. Adjusted corresponding HRs were 1.19 (CI 0.82 to 1.75) and 0.82 (CI 0.46 to 1.46). A subgroup analysis of participants with at least one APOE-epsilon4 allele who entered the study before age 80 produced an adjusted HR of 0.33 (CI 0.10 to 1.04).
Employing time-dependent proportional hazards modeling, the authors found no significant association between statin use and incident dementia or probable AD. In contrast, when the data were analyzed, inappropriately, as a case-control study, the authors found an OR of 0.55 for probable AD, falsely indicating a protective effect of statins. Study design and analytic methods may explain the discrepancy between the current null findings and earlier findings.
在一项有他汀类药物暴露记录和新发痴呆症的前瞻性队列研究中，评估他汀类药物治疗与阿尔茨海默病（AD）风险之间的关联。
这是一项关于他汀类药物使用与新发痴呆症及可能的AD的前瞻性队列研究。从一个健康维护组织（HMO）中随机选取了2356名65岁及以上认知功能正常的人，每两年对其进行痴呆症评估。通过HMO药房数据库确定他汀类药物的使用情况。使用以他汀类药物使用作为时间依存性协变量的比例风险模型来评估他汀类药物与痴呆症/AD之间的关联。
在312名新发痴呆症参与者中，168名可能患有AD。使用他汀类药物时，全因痴呆症的未调整风险比（HRs）为1.33（95%CI 0.95至1.85），可能的AD为0.90（CI 0.54至1.51）。调整后的相应HRs分别为1.19（CI 0.82至1.75）和0.82（CI 0.46至1.46）。对80岁前进入研究的至少携带一个APOE-ε4等位基因的参与者进行亚组分析，调整后的HR为0.33（CI 0.10至1.04）。
通过使用时间依存性比例风险模型，作者发现他汀类药物使用与新发痴呆症或可能的AD之间无显著关联。相比之下，当将数据不恰当地作为病例对照研究进行分析时，作者发现可能的AD的比值比（OR）为0.55，错误地表明他汀类药物具有保护作用。研究设计和分析方法可能解释了当前的阴性结果与早期结果之间的差异。
